Omniox has identified a breakthrough tunable oxygen (O2) delivery technology that perfuses deep into tumors and eliminates hypoxia. Hypoxia, a prominent feature in solid tumors, affects multiple characteristics of tumor cells that lead to higher drug resistance. This proposal describes a series of experiments that will select an optimal candidate that delivers sufficient oxygen to overcome these obstacles, sensitizing neoplastic cells to chemotherapy and greatly improving tumor control. Hypoxic tumor microenvironments harbor cell populations that are pro-tumorigenic, pro-angiogenic and pro-metastatic. While the degree to which these populations overlap remains to be elucidated and may vary between different stages and types of tumors, it is clear that hypoxic tumor cells exhibit high resistance to common chemotherapeutic agents and are thus, likely responsible for tumor reoccurrence and, potentially, metastasis. Consequently, tumor hypoxia has been shown to correlate with poorer patient outcomes in multiple cancer types. Oxygenating hypoxic regions of tumors has the potential to, sensitizing tumors to antineoplastic therapies. Previous efforts to eliminate tumor hypoxia via hyperbaric oxygen, blood transfusions, or inhaled oxygen have not been successful. Even when blood oxygenation is extremely high, hypoxic microenvironments persist due to aberrant tumor blood flow and long diffusion distances that create oxygen gradients from tumor capillaries to hypoxic niches. A different approach is needed to overcome tumor hypoxia, reduce tumor resistance to chemotherapeutic agents and significantly improve treatment outcomes. In this proposal, Omniox is developing a novel set of oxygen carrying proteins to address the tumorigenic issues associated with tumor hypoxia.